Reporter genes have been used to analyze the expression of transgenes from various vectors. Reporter genes that have been used in animal models encode exogenous cytoplasmic or secreted proteins, such as bacterial β-galactosidase, insect luciferase, human growth hormone, human erythropoietin, and human and mouse-secreted alkaline phosphatase (SEAP). These reporter genes often are used for transient expression studies or tissue-specific expression studies. However, the proteins they encode are typically immunogenic. They can also elicit a cytotoxic T-lymphocyte response or a neutralizing antibody response that suppresses detection, leading to inaccurate reporter gene expression data (see Tripathy et al., Nature Medicine 2:545–50 (1996); and Yang et al., Gene Therapy 3:137–44 (1996)).
One reporter gene, the SEAP gene noted above, is derived from the native human placental alkaline phosphatase (hPLAP) (see, Cullen, B. R., and Malim, M. H. Methods Enzymol 216:362–8 (1992)) or mouse embryonic alkaline phosphatase (mSEAP) (see, e.g., U.S. Patent Application Publication 2003/0104422). The amino acid sequence typically used for its reporter gene function differs from the native gene by a deletion of C-terminal residues, which converts the membrane-bound protein into a secreted protein (Berger, et al., Gene 66, 1–10 (1988)).
The art however, has not described a rat SEAP gene. The rat sequence has particular use in studying long term expression in rat because, unlike proteins from other species, it does not induce an immune response. The present application addresses this and other problems.